UCI Authors in PubMed
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Ahn R,Ding YC,Murray J,Fasano A,Green PH,Neuhausen SL,Garner C Department of Epidemiology, University of California Irvine, Irvine, California, United States of America. |
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Association analysis of the extended MHC region in celiac disease implicates multiple independent susceptibility Loci. PLoS One. 2012;7(5):e36926 Celiac disease is a common autoimmune disease caused by sensitivity to the dietary protein gluten. Forty loci have been implicated in the disease. All disease loci have been characterized as low-penetrance, with the exception of the high-risk genotypes in the HLA-DQA1 and HLA-DQB1 genes, which are necessary but not sufficient to cause the disease. The very strong effects from the known HLA loci and the genetically complex nature of the major histocompatibility complex (MHC) have precluded a thorough investigation of the region. The purpose of this study was to test the hypothesis that additional celiac disease loci exist within the extended MHC (xMHC). A set of 1898 SNPs was analyzed for association across the 7.6 Mb xMHC region in 1668 confirmed celiac disease cases and 517 unaffected controls. Conditional recursive partitioning was used to create an informative indicator of the known HLA-DQA1 and HLA-DQB1 high-risk genotypes that was included in the association analysis to account for their effects. A linkage disequilibrium-based grouping procedure was utilized to estimate the number of independent celiac disease loci present in the xMHC after accounting for the known effects. There was significant statistical evidence for four new independent celiac disease loci within the classic MHC region. This study is the first comprehensive association analysis of the xMHC in celiac disease that specifically accounts for the known HLA disease genotypes and the genetic complexity of the region. PMID: 22615847 |
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Krishnan L,Kang A,Sperling G,Srinivasan R Department of Cognitive Sciences, University of California, Irvine, CA, 92617, USA. |
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Neural Strategies for Selective Attention Distinguish Fast-Action Video Game Players. Brain Topogr. 2012 May 22;: We investigated the psychophysical and neurophysiological differences between fast-action video game players (specifically first person shooter players, FPS) and non-action players (role-playing game players, RPG) in a visual search task. We measured both successful detections (hit rates) and steady-state visually evoked EEG potentials (SSVEPs). Search difficulty was varied along two dimensions: number of adjacent attended and ignored regions (1, 2 and 4), and presentation rate of novel search arrays (3, 8.6 and 20 Hz). Hit rates decreased with increasing presentation rates and number of regions, with the FPS players performing on average better than the RPG players. The largest differences in hit rate, between groups, occurred when four regions were simultaneously attended. We computed signal-to-noise ratio (SNR) of SSVEPs and used partial least squares regression to model hit rates, SNRs and their relationship at 3 Hz and 8.6 Hz. The following are the most significant results: RPG players' parietal responses to the attended 8.6 Hz flicker were predictive of hit rate and were positively correlated with it, indicating attentional signal enhancement. FPS players' parietal responses to the ignored 3 Hz flicker were predictive of hit rate and were positively correlated with it, indicating distractor suppression. Consistent with these parietal responses, RPG players' frontal responses to the attended 8.6 Hz flicker, increased as task difficulty increased with number of regions; FPS players' frontal responses to the ignored 3 Hz flicker increased with number of regions. Thus the FPS players appear to employ an active suppression mechanism to deploy selective attention simultaneously to multiple interleaved regions, while RPG primarily use signal enhancement. These results suggest that fast-action gaming can affect neural strategies and the corresponding networks underlying attention, presumably by training mechanisms of distractor suppression. PMID: 22614909 |
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Chen Y,Kushner AM,Williams GA,Guan Z 1] Department of Chemistry, 1102 Natural Sciences 2, University of California, Irvine, California 92697, USA [2]. |
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Multiphase design of autonomic self-healing thermoplastic elastomers. Nat Chem. 2012;4(6):467-72 The development of polymers that can spontaneously repair themselves after mechanical damage would significantly improve the safety, lifetime, energy efficiency and environmental impact of man-made materials. Most approaches to self-healing materials require the input of external energy, healing agents, solvent or plasticizer. Despite intense research in this area, the synthesis of a stiff material with intrinsic self-healing ability remains a key challenge. Here, we show a design of multiphase supramolecular thermoplastic elastomers that combine high modulus and toughness with spontaneous healing capability. The designed hydrogen-bonding brush polymers self-assemble into a hard-soft microphase-separated system, combining the enhanced stiffness and toughness of nanocomposites with the self-healing capability of dynamic supramolecular assemblies. In contrast to previous self-healing polymers, this new system spontaneously self-heals as a single-component solid material at ambient conditions, without the need for any external stimulus, healing agent, plasticizer or solvent. PMID: 22614381 |
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Bhandari A,Gordon W,Dizon D,Hopkin AS,Gordon E,Yu Z,Andersen B Department of Medicine, Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA. |
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The Grainyhead transcription factor Grhl3/Get1 suppresses miR-21 expression and tumorigenesis in skin: modulation of the miR-21 target MSH2 by RNA-binding protein DND1. Oncogene. 2012 May 21;: Epidermal differentiation and stratification, crucial for barrier formation, are regulated by a complex interplay of transcription factors, including the evolutionarily conserved Grainyhead-like 3 (Grhl3/Get1); Grhl3-deleted mice exhibit impaired epidermal differentiation and decreased expression of multiple differentiation genes. To test whether Grhl3 regulates epidermal genes indirectly by controlling the expression of specific microRNAs (miRs), we performed miR profiling and identified 11 miRs that are differentially regulated in Grhl3(-/-) skin, one of which is miR-21, previously shown to be upregulated in diseased skin, including in psoriasis and squamous cell skin cancer. We found that miR-21 is normally expressed in the post-mitotic suprabasal layers of the epidermis, overlapping with Grhl3. The miR-21 promoter is bound and repressed by Grhl3 indicating that these two factors are involved in a regulatory loop maintaining homeostasis in the epidermis. Although miR-21 overexpression in normal keratinocytes had mild effects on the expression of several known miR-21 targets, an enhanced downregulation of the miR-21 tumor-related targets, including MSH2, was observed in Ras-transformed keratinocytes. The increased sensitivity of transformed keratinocytes to miR-21's effects occurs in part through downregulation of the RNA-binding protein DND1 during the transformation process. Additionally, we observed increased tumorigenesis in mice subcutaneously injected with transformed keratinocytes lacking Grhl3. These findings indicate that decreased Grhl3 expression contributes to tumor progression and upregulation of the oncomir miR-21 in squamous cell carcinoma of the skin.Oncogene advance online publication, 21 May 2012; doi:10.1038/onc.2012.168. PMID: 22614019 |
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Greene D,Kang S,Kosenko A,Hoshi N University of California, Irvine, United States. |
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Adrenergic regulation of HCN4 channel requires protein association with beta 2 adrenergic receptor. J Biol Chem. 2012 May 21;: Beta1 and beta2 adrenergic receptors utilize different signaling mechanisms to control cardiac function. Recent studies identified that beta2 adrenergic receptors colocalize with some ion channels which are critical for proper cardiac function. We demonstrate that beta2 adrenergic receptors form protein complexes with a pacemaker channel, HCN4 channel, as well as other subtypes of HCN channels. The adrenergic receptor binding site was identified at a proximal region of the N-terminal tail of the HCN4 channel. Synthetic peptide derived from the beta2 adrenergic receptor binding domain of HCN4 channel disrupted interaction between HCN4 and beta2 adrenergic receptor. In addition, treatment with this peptide prevented adrenergic augmentation of pacemaker currents and spontaneous contraction rate, but did not affect adrenergic regulation of voltage-gated calcium currents. These results suggest that the receptor-ion channel complex is a critical mechanism for ion channel regulation. PMID: 22613709 |
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Mathews MS,Blickenstaff JW,Shih EC,Zamora G,Vo V,Sun CH,Hirschberg H,Madsen SJ University of California, Department of Neurosurgery, Irvine, 101 The City Drive South, Orange, California 92801. |
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Photochemical internalization of bleomycin for glioma treatment. J Biomed Opt. 2012 May;17(5):058001 We study the use of photochemical internalization (PCI) for enhancing chemotherapeutic response to malignant glioma cells in vitro. Two models are studied: monolayers consisting of F98 rat glioma cells and human glioma spheroids established from biopsy-derived glioma cells. In both cases, the cytotoxicity of aluminum phthalocyanine disulfonate (AlPcS2a)-based PCI of bleomycin was compared to AlPcS(2a)-photodynamic therapy (PDT) and chemotherapy alone. Monolayers and spheroids were incubated with AlPcS(2a) (PDT effect), bleomycin (chemotherapy effect), or AlPcS(2a)+bleomycin (PCI effect) and were illuminated (670 nm). Toxicity was evaluated using colony formation assays or spheroid growth kinetics. F98 cells in monolayer/spheroids were not particularly sensitive to the effects of low radiant exposure (1.5 J/cm(2) @ 5 mW/cm(2)) AlPcS(2a)-PDT. Bleomycin was moderately toxic to F98 cells in monolayer at relatively low concentrations-incubation of F98 cells in 0.1 μg/ml for 4 h resulted in 80% survival, but less toxic in human glioma spheroids respectively. In both in vitro systems investigated, a significant PCI effect is seen. PCI using 1.5 J/cm(2) together with 0.25 μg/ml bleomycin resulted in approximately 20% and 18% survival of F98 rat glioma cells and human glioma spheroids, respectively. These results show that AlPcS(2a)-mediated PCI can be used to enhance the efficacy of chemotherapeutic agents such as bleomycin in malignant gliomas. PMID: 22612148 |
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Konecky SD,Owen CM,Rice T,Valdés PA,Kolste K,Wilson BC,Leblond F,Roberts DW,Paulsen KD,Tromberg BJ University of California Irvine, Beckman Laser Institute and Medical Clinic, Laser Microbeam and Medical Program (LAMMP), 1002 Health Sciences Road, Irvine, California 92612. |
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Spatial frequency domain tomography of protoporphyrin IX fluorescence in preclinical glioma models. J Biomed Opt. 2012 May;17(5):056008 Multifrequency (0 to 0.3 mm(-1)), multiwavelength (633, 680, 720, 800, and 820 nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) was used to recover absorption, scattering, and fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating phantoms and in vivo in a mouse model. Three-dimensional tomographic reconstructions of the frequency-dependent remitted light localized the depths of the spheroids within 500 μm, and the total amount of PpIX in the reconstructed images was constant to within 30% when spheroid depth was varied. In vivo tumor-to-normal contrast was greater than ∼1.5 in reduced scattering coefficient for all wavelengths and was ∼1.3 for the tissue concentration of deoxyhemoglobin (ctHb). The study demonstrates the feasibility of SFDI for providing enhanced image guidance during surgical resection of brain tumors. PMID: 22612131 |
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Lin Y,Kwong TC,Bolisay L,Gulsen G University of California, Department of Radiological Sciences, Tu and Yuen Center for Functional Onco-Imaging, Irvine, California 92697. |
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Temperature-modulated fluorescence tomography based on both concentration and lifetime contrast. J Biomed Opt. 2012 May;17(5):056007 It is challenging to image fluorescence objects with high spatial resolution in a highly scattering medium. Recently reported temperature-sensitive indocyanine green-loaded pluronic nanocapsules can potentially alleviate this problem. Here we demonstrate a frequency-domain temperature-modulated fluorescence tomography system that could acquire images at high intensity-focused ultrasound resolution with use of these nanocapsules. The system is experimentally verified with a phantom study, where a 3-mm fluorescence object embedded 2 cm deep in a turbid medium is successfully recovered based on both intensity and lifetime contrast. PMID: 22612130 |
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Coskun PE,Busciglio J Department of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders (iMIND), University of California, Irvine, CA 92697, USA. |
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Oxidative Stress and Mitochondrial Dysfunction in Down's Syndrome: Relevance to Aging and Dementia. Curr Gerontol Geriatr Res. 2012;2012:383170 Genome-wide gene deregulation and oxidative stress appear to be critical factors determining the high variability of phenotypes in Down's syndrome (DS). Even though individuals with trisomy 21 exhibit a higher survival rate compared to other aneuploidies, most of them die in utero or early during postnatal life. While the survivors are currently predicted to live past 60 years, they suffer higher incidence of age-related conditions including Alzheimer's disease (AD). This paper is centered on the mechanisms by which mitochondrial factors and oxidative stress may orchestrate an adaptive response directed to maintain basic cellular functions and survival in DS. In this context, the timing of therapeutic interventions should be carefully considered for the successful treatment of chronic disorders in the DS population. PMID: 22611387 |
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Burkhardt AM,Tai KP,Flores-Guiterrez JP,Vilches-Cisneros N,Kamdar K,Barbosa-Quintana O,Valle-Rios R,Hevezi PA,Zuñiga J,Selman M,Ouellette AJ,Zlotnik A Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA 92697; |
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CXCL17 Is a Mucosal Chemokine Elevated in Idiopathic Pulmonary Fibrosis That Exhibits Broad Antimicrobial Activity. J Immunol. 2012 May 18;: The mucosal immune network is a crucial barrier preventing pathogens from entering the body. The network of immune cells that mediates the defensive mechanisms in the mucosa is likely shaped by chemokines, which attract a wide range of immune cells to specific sites of the body. Chemokines have been divided into homeostatic or inflammatory depending upon their expression patterns. Additionally, several chemokines mediate direct killing of invading pathogens, as exemplified by CCL28, a mucosa-associated chemokine that exhibits antimicrobial activity against a range of pathogens. CXCL17 was the last chemokine ligand to be described and is the 17th member of the CXC chemokine family. Its expression pattern in 105 human tissues and cells indicates that CXCL17 is a homeostatic, mucosa-associated chemokine. Its strategic expression in mucosal tissues suggests that it is involved in innate immunity and/or sterility of the mucosa. To test the latter hypothesis, we tested CXCL17 for possible antibacterial activity against a panel of pathogenic and opportunistic bacteria. Our results indicate that CXCL17 has potent antimicrobial activities and that its mechanism of antimicrobial action involves peptide-mediated bacterial membrane disruption. Because CXCL17 is strongly expressed in bronchi, we measured it in bronchoalveolar lavage fluids and observed that it is strongly upregulated in idiopathic pulmonary fibrosis. We conclude that CXCL17 is an antimicrobial mucosal chemokine that may play a role in the pathogenesis of interstitial lung diseases. PMID: 22611239 |
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Noymer A,Lee R Department of Sociology, University of California, 3151 Social Sciences Plaza, Irvine, CA, 92697-5100, USA, noymer@uci.edu. |
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Immigrant Health Around the World: Evidence from the World Values Survey. J Immigr Minor Health. 2012 May 19;: We describe the relationship between immigrant status and self-rated health around the world, both in raw descriptive statistics and in models controlling for individual characteristics. Using the World Values Survey (1981-2005), we analyze data from 32 different countries worldwide. We estimate four regression models per country. The basic model tests mean differences in self-rated health. Additional models add demographic and social class controls. Introduction of control variables (most particularly, age) changes the results dramatically. In the final model, net of controls, only two countries show poorer immigrant health and three countries show better immigrant health. The multivariate regression models net of controls show few differences in health status between immigrants and the native born. The age structure of immigrant populations is an important mediator of differences in health status compared to the native-born population. PMID: 22610689 |
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Tabuchi H,Borucki E,Berg BG Department of Cognitive Sciences, University of California, Irvine, 2201 Social & Behavioral Sciences Gateway Building, CA 92697-5100, USA. |
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Effects of randomizing phase on the discrimination between amplitude-modulated and quasi-frequency-modulated tones. Hear Res. 2012 May 16;: This study investigated the bandwidth of phase sensitivity. Subjects discriminated amplitude modulated tones (AM), and quasi-frequency modulated tones (QFM) in a two-interval, forced-choice task. An adaptive threshold procedure was used to estimate the modulation depth needed to discriminate the stimuli as a function of carrier and modulation frequency. Non-monotonicities in threshold-bandwidth functions were often observed at higher modulation frequencies. The results are discussed in terms of two potential cues: (1) waveform envelope, (2) cubic distortion products. In order to degrade the information obtained from auditory distortions, the phase for the carrier frequency was randomly sampled from a uniform distribution, which diminished the non-monotonicities with minimal effect at lower modulation frequencies. Model simulations demonstrated that phase randomization degrades distortion product cues with only a modest effect on temporal cues. Final results show that maximum bandwidths for phase sensitivity (BW(max)) were not proportional to carrier frequencies. PMID: 22609773 |
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Donovan KJ,Allen M,Martin RW,Shaka AJ University of California, 1102 Natural Sciences 2, Irvine 92697-2025, United States. |
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Improving the double quantum filtered COSY experiment by "Moving Tube" NMR. J Magn Reson. 2012 Apr 5;219C:41-45 Most 2D NMR spectra show artifacts that become increasingly more prominent as the relaxation delay between transients is decreased. Additionally, "rushing" a 2D experiment may lead to reduced sensitivity. It is shown here how to collect a DQF-COSY spectrum in less time, without artifacts, and with improved sensitivity, by a hardware solution we call Moving Tube NMR (MT NMR): the sample volume is physically moved out of the receiver coil after each transient and replaced by a fresh aliquot that is nearer to the equilibrium magnetization M(0). MT NMR was implemented with an automated mechanism that gave accurate and reproducible vertical tube movement, and a very long 5mm outer diameter (OD) NMR tube to hold a larger sample volume. Comparison of conventional and MT NMR DQF-COSY showed increased sensitivity and far reduced artifacts in the latter. The so-called t(1)-noise in the MT spectrum was no worse than in the conventional spectrum, pointing to the excellent specifications of the long 5mm OD tube, and the good mechanical handling of the automated drive. Thus, MT NMR could improve throughput for routine 2D NMR experiments without reducing sensitivity or adding artifacts, if sufficient sample is available. MT NMR could also be useful in cases of limited solubility, or for nuclei with long T(1) relaxation times. PMID: 22609524 |
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Chen G,Meng L,Alexander B,Tran NP,Kain ZN,Cannesson M Department of Anesthesiology & Perioperative Care, University of California, Irvine, CA 92868, USA; Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, P. R. China. |
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Comparison of noninvasive cardiac output measurements using the Nexfin monitoring device and the esophageal Doppler. J Clin Anesth. 2012 Jun;24(4):275-83 To evaluate the validity of cardiac output (CO) measurements obtained using the Nexfin device in comparison to those obtained with the esophageal Doppler in steady-state conditions and after phenylephrine administration. PMID: 22608581 |
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Weber JJ,Goodwillie C Department of Ecology & Evolutionary Biology, University of California, Irvine, California, CA, USA Department of Biology, East Carolina University, Greenville, NC, USA. |
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Variation in floral longevity in the genus Leptosiphon: mating system consequences. Plant Biol (Stuttg). 2012 May 18;: Pollination or fertilisation trigger floral senescence in a wide range of flowering plants, and yet little attention has been given to the implications of this phenomenon to mating system evolution. We examined the effects of pollination on floral senescence in the genus Leptosiphon. Species in the genus exhibit a wide range of breeding systems. In all cases, compatible pollination induced senescence; emasculated flowers lived longer than hand-outcrossed flowers. In the self-compatible species, Leptosiphon acicularis and L. bicolor, and in one highly selfing population of L. jepsonii, unmanipulated flowers had reduced longevity compared to emasculated flowers, suggesting that autonomous self-pollination limits floral longevity in these species. Limited floral longevity in these highly selfing taxa may reduce opportunities for male outcross success, representing a possible source of selection on the mating system. In turn, the mating system might influence how selection acts on floral longevity; obligately outcrossing taxa are expected to benefit from longer floral longevities to maximise opportunities for pollination, while selfing taxa might benefit from earlier floral senescence to reduce resource expenditure. Overall, the longevity of unpollinated flowers increased with the level of outcrossing in the genus Leptosiphon. Our results taken together with those of a previous study and similar results in other species suggest that floral longevity may represent a largely unexamined role in mating system evolution. PMID: 22607097 |
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Kayala MA,Baldi P Department of Computer Science and Institute for Genomics and Bioinformatics, University of California, Irvine. Irvine, CA 92697, USA. |
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Cyber-T web server: differential analysis of high-throughput data. Nucleic Acids Res. 2012 May 16;: The Bayesian regularization method for high-throughput differential analysis, described in Baldi and Long (A Bayesian framework for the analysis of microarray expression data: regularized t-test and statistical inferences of gene changes. Bioinformatics 2001: 17: 509-519) and implemented in the Cyber-T web server, is one of the most widely validated. Cyber-T implements a t-test using a Bayesian framework to compute a regularized variance of the measurements associated with each probe under each condition. This regularized estimate is derived by flexibly combining the empirical measurements with a prior, or background, derived from pooling measurements associated with probes in the same neighborhood. This approach flexibly addresses problems associated with low replication levels and technology biases, not only for DNA microarrays, but also for other technologies, such as protein arrays, quantitative mass spectrometry and next-generation sequencing (RNA-seq). Here we present an update to the Cyber-T web server, incorporating several useful new additions and improvements. Several preprocessing data normalization options including logarithmic and (Variance Stabilizing Normalization) VSN transforms are included. To augment two-sample t-tests, a one-way analysis of variance is implemented. Several methods for multiple tests correction, including standard frequentist methods and a probabilistic mixture model treatment, are available. Diagnostic plots allow visual assessment of the results. The web server provides comprehensive documentation and example data sets. The Cyber-T web server, with R source code and data sets, is publicly available at http://cybert.ics.uci.edu/. PMID: 22600740 |
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Wagner LO,Stoudenmire EM,Burke K,White SR Department of Physics and Astronomy, University of California, Irvine, CA 92697, USA. lwagner@uci.edu. |
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Reference electronic structure calculations in one dimension. Phys Chem Chem Phys. 2012 May 17;: Large strongly correlated systems provide a challenge to modern electronic structure methods, because standard density functionals usually fail and traditional quantum chemical approaches are too demanding. The density-matrix renormalization group method, an extremely powerful tool for solving such systems, has recently been extended to handle long-range interactions on real-space grids, but is most efficient in one dimension where it can provide essentially arbitrary accuracy. Such 1d systems therefore provide a theoretical laboratory for studying strong correlation and developing density functional approximations to handle strong correlation, if they mimic three-dimensional reality sufficiently closely. We demonstrate that this is the case, and provide reference data for exact and standard approximate methods, for future use in this area. PMID: 22596085 |
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Campione S,Capolino F Department of Electrical Engineering and Computer Science, University of California Irvine, CA 92697-2625, USA. |
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Composite material made of plasmonic nanoshells with quantum dot cores: loss-compensation and ε-near-zero physical properties. Nanotechnology. 2012 May 17;23(23):235703 A theoretical investigation of loss-compensation capabilities in composite materials made of plasmonic nanoshells is carried out by considering quantum dots (QDs) as the nanoshells' cores. The QD and metal permittivities are modeled according to published experimental data. We determine the modes with real or complex wavenumber able to propagate in a 3D periodic lattice of nanoshells. Mode analysis is also used to assess that only one propagating mode is dominant in the composite material whose optical properties can hence be described via homogenization theory. Therefore, the material effective permittivity is found by comparing different techniques: (i) the mentioned mode analysis, (ii) Maxwell Garnett mixing rule and (iii) the Nicolson-Ross-Weir method based on transmission and reflection when considering a metamaterial of finite thickness. The three methods are in excellent agreement, because the nanoshells considered in this paper are very subwavelength, thus justifying the parameter homogenization. We show that QDs are able to provide loss-compensated ε-near-zero metamaterials and also loss-compensated metamaterials with large negative values of permittivity. Besides compensating for losses, the strong gain via QD can provide optical amplification with particular choices of the nanoshell and lattice dimensions. PMID: 22595780 |
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Kimonis VE,Steller J,Sahai I,Grange DK,Shoemaker J,Zelaya BM,Mandell R,Shih K,Shih V Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, CA, USA; Division of Genetics, Department of Pediatrics, Southern Illinois University School of Medicine, Springfield, IL, USA. |
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Mild fumarase deficiency and a trial of low protein diet. Mol Genet Metab. 2012 Apr 20;: We report clinical findings in a 12-year-old girl with a mild case of fumarase deficiency who continues to make progress. She has two novel mutations of the fumarase gene [c.521C>G (p.P174R) and c.908T>C (p.L303S)]. A trial of low protein diet did not reduce fumaric aciduria. PMID: 22595425 |
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Seiler MJ,Jones BW,Aramant RB,Yang PB,Keirstead HS,Marc RE Anatomy & Neurobiol/Reeve-Irvine Research Center, UC Irvine, Irvine, CA 92697-4265, USA Sue & Bill Gross Stem Cell Research Center, UC Irvine, Irvine, CA, USA Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, UT, USA. |
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Computational molecular phenotyping of retinal sheet transplants to rats with retinal degeneration. Eur J Neurosci. 2012 May 17;: Retinal progenitor sheet transplants have been shown to extend neuronal processes into a degenerating host retina and to restore visual responses in the brain. The aim of this study was to identify cells involved in transplant signals to retinal degenerate hosts using computational molecular phenotyping (CMP). S334ter line 3 rats received fetal retinal sheet transplants at the age of 24-40 days. Donor tissues were incubated with slow-releasing microspheres containing brain-derived neurotrophic factor or glial cell-derived neurotrophic factor. Up to 265 days after surgery, eyes of selected rats were vibratome-sectioned through the transplant area (some slices stained for donor marker human placental alkaline phosphatase), dehydrated and embedded in Eponate, sectioned into serial ultrathin datasets and probed for rhodopsin, cone opsin, CRALBP (cellular retinaldehyde binding protein), l-glutamate, l-glutamine, glutathione, glycine, taurine, γ-aminobutyric acid (GABA) and DAPI (4',6-diamidino-2-phenylindole). In large transplant areas, photoreceptor outer segments in contact with host retinal pigment epithelium revealed rod and cone opsin immunoreactivity whereas no such staining was found in the degenerate host retina. Transplant photoreceptor layers contained high taurine levels. Glutamate levels in the transplants were higher than in the host retina whereas GABA levels were similar. The transplant inner nuclear layer showed some loss of neurons, but amacrine cells and horizontal cells were not reduced. In many areas, glial hypertrophy between the host and transplant was absent and host and transplant neuropil appeared to intermingle. CMP data indicate that horizontal cells and both glycinergic and GABAergic amacrine cells are involved in a novel circuit between transplant and host, generating alternative signal pathways between transplant and degenerating host retina. PMID: 22594836 |
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Chen H,Takemoto R,Hata J UCI Medical Center, Orange, California, USA. |
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Ultrasound Guided Piriformis Injection with Confirmation of Needle Placement Through Electromyography. Pain Med. 2012 May 17;: PMID: 22594766 |
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Tatarenkov A,Earley RL,Taylor DS,Avise JC *Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697, USA; Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USA; Brevard County Environmentally Endangered Lands Program, Melbourne, FL 32904, USA. |
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Microevolutionary Distribution of Isogenicity in a Self-fertilizing Fish (Kryptolebias marmoratus) in the Florida Keys. Integr Comp Biol. 2012 May 15;: The mangrove rivulus Kryptolebias marmoratus and a closely related species are the world's only vertebrates that routinely self-fertilize. Such uniqueness presents a model for understanding why this reproductive mode, common in plants and invertebrates, is so rare in vertebrates. A survey of 32 highly polymorphic loci in >200 specimens of mangrove rivulus from multiple locales in the Florida Keys, USA, revealed extensive population-genetic structure on microspatial and micro-temporal scales. Observed heterozygosities were severely constrained, as expected for a hermaphroditic species with a mixed-mating system and low rates of outcrossing. Despite the pronounced population structure and the implied restrictions on effective gene flow, isogenicity (genetic identity across individuals) within and among local inbred populations was surprisingly low even after factoring out probable de novo mutations. Results indicate that neither frequent bottlenecks nor directional genetic adaptation to local environmental conditions were the primary driving forces impacting multilocus population-genetic architecture in this self-fertilizing vertebrate species. On the other hand, a high diversity of isogenic lineages within relatively small and isolated local populations is consistent with the action of diversifying selection driven by the extreme spatio-temporal environmental variability that is characteristic of mangrove habitats. PMID: 22593558 |
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Vonholdt BM,Takuno S,Gaut BS University of California, Irvine; Ecology and Evolutionary Biology; Irvine, CA 92697-2525; Department of Plant Sciences, University of California, Davis, California 95616, USA. |
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Recent retrotransposon insertions are methylated and phylogenetically clustered in japonica rice (Oryza sativa spp. japonica). Mol Biol Evol. 2012 May 15;: In plants, the genome of the host responds to the amplification of transposable elements (TEs) with DNA methylation. However, neither the factors involved in TE methylation nor the dynamics of the host-TE interaction are well resolved. Here we identify 5522 long terminal repeat retrotransposons (LRT-RT) in the genome of Oryza sativa ssp. japonica and then assess methylation for individual elements. Our analyses uncover three strong trends: long LTR-RTs are more highly methylated, the insertion time of LTR-RTs are negatively correlated with methylation, and young LTR-RTs tend to be closer to genes than older insertions. Additionally, a phylogenetic examination of the gypsy-like LTR-RT superfamily revealed that methylation is phylogenetically correlated. Given these observations, we present a model suggesting that the phylogenetic correlation among related LTR-RTs is a primary mechanism driving methylation. In this model, bursts of transposition produce new elements with high sequence similarity. The host machinery identifies proliferating elements as well closely related LTR-RTs through cross-homology. In addition, our data are consistent with previous hypotheses that methylated LTR-RT elements are removed preferentially from regions near genes, explaining some of the observed age distribution. PMID: 22593226 |
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Mathews MS,Vo V,Shih EC,Zamora G,Sun CH,Madsen SJ,Hirschberg H Department of Neurological Surgery, University of California Irvine, Orange, CA ; Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, CA. |
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Photochemical internalization-mediated delivery of chemotherapeutic agents in human breast tumor cell lines. J Environ Pathol Toxicol Oncol. 2012;31(1):49-59 Breast-conservation surgery (BCS) is now utilized in patients with stage I and II invasive breast cancer. However, positive surgical margins are associated with recurrence, and therefore some form of localized postoperative therapy (radiation/chemotherapy) is necessary to eliminate remaining cancer cells. Existing modalities have significant treatment-limiting side effects; therefore, alternative forms of localized therapy need to be explored. We studied the ex vivo effects of photochemical internalization (PCI) using 4 chemotherapeutic agents: cisplatin, cisplatin analog [D prostanoid, DP], doxorubicin, and bleomycin) on 3 breast cancer cell lines: MCF-7, MDA-MB-435, and MDA-MB-231. Illumination was carried out using a 670-nm diode laser at 5 mW/cm2 following incubation in the photosensitizer with aluminum phthalocyanine disulfonate. Toxicity was investigated using colony-forming assays and the mechanism of cell death was determined using Annexin flow-cytometry. We found that toxicity of DP and bleomycin was significantly enhanced by PCI compared with drug alone but was unchanged for cisplatin and doxorubicin. PCI treatment caused a decrease in the percentage of viable cells, predominantly by enhancing apoptosis. The action was synergistic across all 3 cell lines tested for DP and bleomycin. Thus, with appropriate delivery devices and choice of chemotherapeutic agents, PCI holds the promise of enhancing tumor cell toxicity surrounding the cavity of BCS resection sites and thereby decreasing local recurrence. PMID: 22591284 |
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Chandraratna PA,Mohar DS,Sidarous PF,Brar P,Miller J,Shah N,Kadis J,Ali A,Mohar P Division of Cardiology, Long Beach VA Medical Center, UC Irvine School of Medicine, Irvine, California. |
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Evaluation of Non-ST Segment Elevation Acute Chest Pain Syndromes with a Novel Low-Profile Continuous Imaging Ultrasound Transducer. Echocardiography. 2012 May 17;: Background: This investigation was designed to test the hypothesis that continuous cardiac imaging using an ultrasound transducer developed in our laboratory (ContiScan) is superior to electrocardiogram (ECG) monitoring in the diagnosis of coronary artery disease (CAD) in patients with acute non-ST segment elevation chest pain syndromes. Methods: Seventy patients with intermediate to high probability of CAD who presented with typical anginal chest pain and no evidence of ST segment elevation on the ECG were studied. The 2.5-MHz transducer is spherical in its distal part mounted in an external housing to permit steering in 360 degrees. The transducer was placed at the left sternal border to image the left ventricular short-axis view and recorded on video tape at baseline, during and after episodes of chest pain. Two ECG leads were continuously monitored. The presence of CAD was confirmed by coronary arteriography or nuclear or echocardiographic stress testing. Results: Twenty-four patients had regional wall motion abnormalities (RWMA) on their initial echo which were unchanged during the period of monitoring. All had evidence of CAD. Twenty-eight patients had transient RWMA. All had evidence of CAD. Eighteen patients had normal wall motion throughout the monitoring period, 14 of these had no evidence of CAD, and four had evidence of CAD. These four patients did not have chest pain during monitoring. The sensitivity, specificity, and accuracy of echocardiographic monitoring for diagnosing non-ST elevation myocardial infarction was 88%, 100%, and 91% respectively. The sensitivity, specificity, and accuracy of the ECG for diagnosis of CAD were 31%, 100%, and 52%, respectively. Echocardiography was superior to ECG (P < 0.001). Conclusions: The data indicate that continuous cardiac imaging is superior to ECG monitoring for the diagnosis of CAD in patients presenting with acute non-ST segment elevation chest pain syndromes. This technique could be a useful adjunct to ECG monitoring for myocardial ischemia in the acute care setting. (Echocardiography, 2012;**:1-5). PMID: 22591210 |
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